A goal of this research project is to isolate genes undergoing unique epigenetic regulation to give monoallelic expression. In general, epigenetic phenomena that achieve dosage control fall into three categories: 1) random X chromosome inactivation in female, 2) parental specific imprinting of selected autosomal genes, and 3) random autosomal inactivation, e.g. immunoglobulin and olfactory receptor genes. We have recently identified three new genes that belong to this third category. These genes showed hemizygously methylated CpG sites by Southern blot analyses, and primarily monoallelic expression by single cell allele-specific RT-PCR analysis of bone marrow stromal cells and hepatocytes. Unlike other genes previously placed in this category, these three genes exist as a tight cluster, in the proximal region of mouse chromosome 17. They thus provide the first example of a region of autosomal random monoallelic expression. Further analyses of these genes are underway.